Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-2, pokeweed mitogen, and lipopolysaccharide were evaluated for their ability to accelerate involution and to stimulate local cellular defenses in the nonlactating bovine mammary gland. Twelve cows were divided into three treatment groups of 4 cows each to receive interleukin-2, pokeweed mitogen, or lipopolysaccharide. One day after drying off, 3 mammary quarters of each cow were infused with 100 micrograms of immunostimulant daily for 21 d; the remaining control quarter received PBS. Secretion samples were collected weekly to determine bacteriologic status, total SCC, and differential cell counts. On d 21, cows were killed, and tissues were collected for microscopy. Overall, SCC were higher in immunostimulated quarters, but only those infused with interleukin-2 were significantly elevated over controls. By wk 3, the percentage of neutrophils decreased in interleukin-2 and pokeweed mitogen quarters over pretreatment values, percentage of macrophages increased in interleukin-2 quarters, and percentage of lymphocytes increased in pokeweed mitogen and lipopolysaccharide quarters. Percentage of alveolar lumina was reduced, and connective tissue stroma increased, in all immunostimulated quarters compared with those of controls, suggesting accelerated involution. Involution was greatest in quarters treated with interleukin-2. Leukocyte infiltration was greater in immunostimulated quarters than in control quarters. Similarly, concentrations of Ig-producing plasma cells were greater in immunostimulated quarters than in control quarters. Quarters infused with interleukin-2 exhibited the greatest concentration of plasma cells, followed by quarters treated with pokeweed mitogen and lipopolysaccharide; IgG1 plasma cells predominated, followed by IgG2, IgA, and IgM. Interleukin-2 accelerated involution and stimulated local antibody production more than did the two mitogens, suggesting a potential role for this cytokine as a general immunostimulant at drying off.
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PMID:The effect of chronic immunostimulation of the nonlactating bovine mammary gland with interleukin-2, pokeweed mitogen, and lipopolysaccharide. 147 3

The purpose of this study was to compare the local and systemic therapeutic effects of Interleukin-2 (IL-2) used in 3 different preparations: suspended in PBS, suspended in 2% agar, and entrapped in multi-lamellar liposomes suspended in 2% agar. The liposomes were composed of phosphatidylglycerol and phosphatidylcholine in a 1:4 molar ratio. The net release of IL-2 in vitro (by ELISA assay) at 37 degrees C, measured at 4 hr, 2 days, and 10 days, was 50%, 75%, and 100% from agar, and 8%, 22%, and 33% from liposomes in agar. In the therapeutic tests, the IL-2 preparations were injected close to s.c. implants of the MC2 mouse mammary carcinoma. Four injections at weekly intervals of IL-2 in agar had as much local and systemic (against uninjected contralateral tumor implants in treated mice) therapeutic effect as the same total amount of IL-2 in PBS given in 20 daily injections over 4 weeks. The IL-2 liposome-gel preparation was most effective (p less than 0.05), probably due to the more sustained release of IL-2. Three injections of this preparation gave a fixed and sustained peritumor release of IL-2 which, at sub-toxic levels, resulted in both local and systemic therapeutic effects.
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PMID:Immunotherapy of a mouse mammary carcinoma by sustained peritumor release of IL-2. 199 85

The antileukemic effects of lymphokine-activated killer (LAK) cells plus recombinant interleukin-2 (rIL-2) therapy were assessed in mice with Friend virus (FV)-induced erythroleukemia. LAK cells were generated by incubating normal spleen cells for 72 hr in the presence of rIL-2 (1000 units/ml). At the time of injection, the LAK cells were cytotoxic in vitro against FV-infected fibroblasts and NK-sensitive and -resistant tumor targets but not normal controls. To determine in vivo activity, fully leukemic mice (spleen weight greater than 0.75 g) were injected with either PBS or LAK cells (10(8) cells/mouse IV at 14 and 17 days post virus) and rIL-2 (10,000 units/mouse IP every 8 hr on days 14 through 18 post virus). More than 70% of the progressively leukemic mice experienced permanent leukemia regressions (disease-free for greater than 100 days) following LAK cell plus rIL-2 therapy. Regressions were characterized by return of spleen and liver weights to normal and elimination of virus-infected erythroid (CFU-E) and macrophage (CFU-C) progenitor cells from spleen and marrow. Leukemic animals treated with either LAK cells alone or IL-2 alone experienced only transient leukemia regressions. These results demonstrate that LAK cell plus rIL-2 treatment can induce permanent regressions in progressively leukemic mice and provide a responsive and manipulable model system to elucidate the mechanisms involved in this form of immunotherapy.
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PMID:Lymphokine-activated killer cell plus recombinant interleukin-2 therapy of erythroleukemia in mice. 278 72

Interleukin-2 (IL-2) prepared from Con A-activated rat spleen cells was partially purified using hydroxylapatite chromatography (HTP) and chromatofocusing on Mono P. IL-2 eluted in a major peak between 0.1 and 0.25 M NaCl in PBS (purification factor 36-fold) and in a second peak in the high salt elution (purification factor 5-fold). When analysed on Mono P, the major peak was found to resolve into four components with apparent pI values in the range of 7.05-5.80; further activity eluted in the high salt fraction. Similar patterns were observed using high salt eluted activity with minor variations in the apparent pI values. Neuraminidase treatment caused a shift in IL-2 charge towards more basic pI values. This analysis of the multiple species of IL-2 suggests that part of the heterogeneity may be due to variation in the degree of sialylation of the peptide chain.
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PMID:Heterogeneity of rat TCGF defined by Mono P isoelectric focusing. 661 Jan 4

Recombinant bovine interleukin-2 was tested as adjunct therapy to intramammary infusion of antibiotics at drying off. Cows were assigned randomly within three commercial herds to either recombinant bovine interleukin-2 or PBS treatment groups at drying off. Ninety-five cows received intramammary infusions of 1 mg of recombinant bovine interleukin-2 in each quarter immediately preceding intramammary infusion of a product for antibiotic therapy of dry cows. Ninety-four cows received intramammary infusion of 10 ml of endotoxin-free PBS in each quarter immediately preceding the antibiotic therapy. Cure rates for IMI present at drying off did not differ between cows treated with recombinant bovine interleukin-2 and those treated with PBS. Intramammary infusion of recombinant bovine interleukin-2 did not affect the rate of new IMI during the dry period. Milk production and SCC during the first 3 mo of lactation subsequent to therapy did not differ between treatment groups. Intramammary infusion of recombinant bovine interleukin-2 was not effective as an adjunct to antibiotic therapy for dry cows.
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PMID:Efficacy of recombinant bovine interleukin-2 as an adjunct to dry cow therapy. 762 17

We examined the ability of anti-human recombinant interleukin-2 (hu rIL-2) monoclonal antibody DMS-1.10 to increase serum half-life of hu rIL-2, and the effect of this complex on inhibition of tumor progression in a B16-F10 murine melanoma model. In C57B1/6 mice, intravenous (i.v.) injection of DMS-1.10 premixed with 1 x 10(4) units (U) of hu rIL-2 at a 1:1 molar ratio extended serum half-life greater than 10-fold (222 min) when compared to the same dose of hu rIL-2 alone (20 min). In a murine tumor model, multiple intraperitoneal (i.p.) injections of non-neutralizing DMS-1.10 premixed with hu rIL-2 at a 5:1 molar ratio reduced the growth rate of subcutaneous (s.c.) B16-F10 tumor in C57B1/6 mice by 64% when compared to PBS and irrelevant antibody treated controls. Although similar treatment with hu rIL-2 alone reduced tumor growth rate by 46%, it was significantly less effective than the premixed treatment. Results from a flow cytometry assay confirm B16-F10 does not have IL-2 receptors, precluding direct inhibition of tumor growth by hu rIL-2 treatments. We propose that therapeutic efficacy of hu rIL-2 is improved by prolonging the in vivo half-life with an anti-IL-2 antibody, thus augmenting hu rIL-2 bioactivity and enhancing the hosts immune response against tumor.
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PMID:An anti-IL-2 antibody increases serum half-life and improves anti-tumor efficacy of human recombinant interleukin-2. 785 53

AKR/J mice, highly susceptible to spontaneous T cell leukemogenesis, were protected from developing the disease by H-2-compatible allogenic bone marrow transplantation (BMT) and intermittent treatment with interleukin-2(IL-2). Allogeneic BMT from C3H/HeJ mice and treatment with PBS yielded T cell leukemia in chimeras after the same latent period as that observed in normal AKR/J mice. In contrast, IL-2-treated chimeras caused an incidence of only 40% T cell leukemia. The preventing effect of IL-2 on leukemia development was not observed in one-year-treated chimeras, probably due to a lack of continuous antileukemic effects over the long term. Both LAK and NK activities in spleen cells were significantly increased in IL-2-treated chimeras. The cytotoxicity against T cell lymphoma cell line derived from AKR/J also increased in the IL-2-treated chimeras. Similarly, LPS-, PWM-, and IL-2-induced responses were increased in the IL-2-treated chimeras. TNF-alpha secretion from spleen cells also rose after IL-2-administration. IL-1 beta, IFN-gamma, and TNF-alpha mRNA became detectable in spleen cells using the PCR technique. The characteristics of leukemia cells in chimeras with overt leukemia were not directly affected by IL-2 administration. It is suggested that partial inhibition of spontaneous T cell leukemia development in AKR/J mice by allogeneic BMT and IL-2 may be due to the enhancement of graft-versus-leukemia effects. Further study may provide insights into the mechanisms involved in preventing leukemia development after allogenic BMT and IL-2 in AKR/J mice.
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PMID:Antileukemic effect of interleukin-2 on spontaneous development of leukemia after H-2-compatible allogenic bone marrow transplantation in AKR/J mice. 792 84

The efficacy of tumor therapy using polyethylene-glycol-modified interleukin-2 (PEG-IL-2), alone or in combination with cyclophosphamide, was studied in advanced metastatic disease in the guinea pig. Line 10 (L10) tumor cells appeared in the axillary lymph node only 7 days after intradermal tumor-cell inoculation, and lymph-node leukocytes were almost completely replaced by tumor cells on day 28. Local treatment of the intradermally growing L10 hepatocarcinoma in the guinea pig with a relatively low dose of PEG-IL-2 resulted in regression of the primary tumor and prevention of lymph-node metastases. Therapy was completely curative (4 out of 5 animals) when started on day 7 or 14 after tumor-cell inoculation. When started on day 21, therapy was effective in only some (2 out of 5 cured) of the treated animals. Anti-tumor effects against the primary tumor and against lymph-node metastases were observed only after intratumoral (i.t.) administration of PEG-IL-2. Injection of the agent into or near lymph-node metastases in the absence of the primary tumor had no curative effect. In PBS/BSA-treated control animals the primary tumor and metastases grew progressively. In the treatment of far advanced metastatic disease, the combination of i.t. administration of PEG-IL-2 and i.p. injection of cyclophosphamide (Cy) resulted in improved anti-tumoral effects (5/5 guinea pigs were cured) when compared with monotherapy using either agent (one and none out of 5 animals cured, respectively). PBS/BSA heated controls showed progressive tumor-growth. We conclude that large primary tumors and lymph-node metastases can be treated effectively with PEG-IL-2. The i.t. route of administration is of major importance in the treatment of metastases, since administration of PEG-IL-2 near or into the lymph node had no therapeutic effect. Combination of PEG-IL-2 therapy with systemic injections of Cy significantly improved the curative effects of the treatment of advanced metastatic cancer.
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PMID:PEG-IL-2 therapy of advanced cancer in the guinea pig. Impact of the primary tumor and beneficial effect of cyclophosphamide. 792 81

The histologic and cytologic responses of heifer mammary glands infected with Staphylococcus aureus were studied after infusion of interleukin-2 or interferon-gamma. Two groups of 4 heifers each, which were infected experimentally with S. aureus in all 4 mammary quarters, were infused in diagonal quarters with 7.5 x 10(5) units of interleukin-2 or 10(5) units of interferon-gamma; remaining quarters received PBS. Heifers in both trials were slaughtered 14 d after cytokine infusion, and mammary tissues were collected for histological examination. Uninfected quarters from 2 additional heifers were left untreated to compare infected with uninfected tissues for both trials. Morphologic evaluation and leukocyte infiltration scores were performed on tissue sections stained with hematoxylin and eosin, and plasma cells were quantified on sections stained with immunoperoxidase. Infected quarters had lower percentages of alveolar epithelial and luminal areas and higher percentages of stromal area than did uninfected quarters in the interleukin-2 trial, but no differences were observed between infected quarters that had been treated with PBS or interleukin-2. Likewise, interferon-gamma treatment had no effect on mammary parenchymal components in the infected quarters. Interleukin-2 treatment significantly elevated leukocytosis into the mammary gland parenchyma compared with infected quarters treated with PBS and uninfected quarters. Among the leukocyte types evaluated, eosinophilic infiltration was elevated in interleukin-2 quarters over that of PBS controls. In both trials, concentrations of plasma cells bearing Ig were elevated in infected versus uninfected quarters. Plasma cell concentrations also were higher in cytokine than PBS controls, especially in interleukin-2 quarters. Results suggested that neither cytokine influenced the histology of infected mammary tissues, but both interleukin-2 and interferon-gamma increased, although insignificantly, the prevalence of all isotypes of plasma cells bearing Ig, suggesting enhancement of the local immune response to IMI.
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PMID:Histologic response of the heifer mammary gland to intramammary infusion of interleukin-2 or interferon-gamma. 822 19

In previous studies we have induced TSH binding-inhibiting Igs and thyroiditis in BALB/c mice and thyroiditis alone in NOD mice immunized with the extracellular domain of the human TSH receptor produced as a maltose-binding protein fusion in bacteria (MBP-ECD). In this study, our aim was to determine whether thyroiditis can be transferred to syngeneic naive recipients with in vivo and in vitro primed spleen cells. Groups of 6-week-old female BALB/c and NOD mice were immunized ip with MBP-ECD in an adjuvant of alum plus attenuated Bordetella pertussis toxin, on days 0 (100 micrograms), 14, 28, and 35 (50 micrograms). These mice (in vivo primed) and nontreated age- and sex-matched controls were killed on day 43, and their spleens and thyroids were removed, the latter to verify the induction of thyroiditis in the antigen-treated mice. Splenocytes were disrupted mechanically and cultured at 3 x 10(6)/ml in RPMI supplemented with 20 micrograms/ml MBP-ECD for 48-64 h. After this in vitro priming, some of the splenocytes received no further treatment, but a portion was fractionated into a CD4+-enriched population. Groups of 6-week-old female BALB/c and NOD mice were immunized into the tail vein with 100-200 microliters PBS containing approximately 10(5)-10(7) unfractionated T cells (both in vivo primed and not) and CD4+-enriched (in vivo primed) splenocyte populations. The animals were killed 16 days later, and their thyroids were examined histologically and by immunohistochemistry. In addition, levels of antibody to the MBP-ECD priming antigen were assessed by enzyme-linked immunosorbent assay in the antigen- and spleen-treated mice. In the donor animals, in vivo priming resulted in an extensive lymphocytic infiltration of the thyroids in both BALB/c and NOD mice and follicular destruction in the latter. There was no evidence of thyroiditis in all 9 BALB/c mice and all 4 NOD mice who received unfractionated T cells from mice that had not been primed in vivo. In contrast, transfer of MBP-ECD in vivo primed unfractionated T cells resulted in thyroiditis in 9 of 13 BALB/c mice and 5 of 6 NOD mice; similarly, the equivalent CD4+-enriched population produced extensive thyroiditis in 2 of 3 BALB/c mice and all three NOD mice. The most striking difference between the antigen- and spleen-treated mice was in the quantity of the infiltrate, which was much greater in the latter and extended throughout the thyroid glands of these animals. In common with mice treated directly with the MBP-ECD antigen, the infiltrates of both BALB/c and NOD recipient mice contained large numbers of activated T cells expressing the receptor for interleukin-2, and macrophages and dendritic cells were plentiful, particularly in the BALB/c mice, in which B cells and interleukin-10-positive T cells were also present. The most abundant infiltrates, containing numerous CD8+ T cells and follicular destruction, were observed in NOD mice receiving primed unfractionated T cells or CD4+-enriched T cells. In contrast to the donors, none of the recipient animals had circulating antibodies to the MBP-ECD antigen. In conclusion, we have shown that it is possible to transfer thyroiditis with spleen cells from mice primed in vivo with a human TSH receptor preparation. Furthermore, the thyroiditogenic activity appears to reside in the CD4+ population.
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PMID:Transfer of thyroiditis, with syngeneic spleen cells sensitized with the human thyrotropin receptor, to naive BALB/c and NOD mice. 889 27


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